CD30 CAR T-Cells for Testicular Cancer

Overseen by Matthew Milowsky, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Pregnancy, HIV, Hepatitis B, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment to fight certain types of cancer in adults. The treatment aims to improve how the body targets and kills cancer cells. Researchers will collect samples to see how well the treatment works and lasts in the body.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the idea that CD30 CAR T-Cells for Testicular Cancer is an effective treatment?

The available research shows that CD30 CAR T-Cells have demonstrated antitumor activity against embryonal carcinomas, a type of testicular cancer, in both laboratory and animal studies. These cells were able to target and kill cancer cells that express the CD30 marker, as well as nearby cancer cells that do not express this marker, through a special interaction. This suggests that CD30 CAR T-Cells could be a promising treatment for testicular cancer, especially for aggressive types that are difficult to treat with standard therapies. ^{1 2 3 4 5}

What safety data is available for CD30 CAR T-Cell therapy in testicular cancer?

The safety data for CD30 CAR T-Cell therapy, while not specific to testicular cancer, can be inferred from general CAR T-Cell studies. CAR T-Cell therapies, including those targeting CD30, have shown potential in treating hematologic malignancies with some success. However, they are associated with risks such as cytokine release syndrome, neurotoxicity, and 'on-target off-tumor' effects, where healthy cells expressing the target antigen may also be affected. Strategies to mitigate these risks, such as pharmacologic interventions and suicide genes, are under investigation. CD30 CAR T-Cells have been noted to spare CD30+ hematopoietic stem cells while targeting lymphoma cells, suggesting a level of safety in targeting CD30. Overall, while promising, CAR T-Cell therapies require careful management of potential toxicities. ^{6 7 8 9 10}

Is the treatment ATLCAR.CD30 Cells a promising treatment for testicular cancer?

Yes, ATLCAR.CD30 Cells, which are a type of CAR T-cell therapy, show promise for treating testicular cancer. They can target and kill cancer cells that have the CD30 marker, and they can also attack nearby cancer cells that don't have this marker. This makes them a strong candidate for treating aggressive forms of testicular cancer. ^{1 4 5 11 12}

Research Team

Matthew Milowsky, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

Adults over 18 with Nonseminomatous Germ Cell Tumors (NSGCT) who've had at least one prior treatment can join. They must show tumor growth or elevated cancer markers after high-dose chemo. Pregnant women, those breastfeeding, and individuals with active HIV, HTLV, hepatitis B or C are excluded.

Inclusion Criteria

I am 18 years old or older.

My cancer is a type of germ cell tumor that is not seminoma.

I have had at least one treatment for my non-seminoma germ cell tumor.

Exclusion Criteria

I do not have active HIV, HTLV, hepatitis B, or hepatitis C infections.

Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated in the study).

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Administration of autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) to subjects with CD30+ Nonseminomatous Germ Cell Tumors

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of overall response rate and progression-free survival

12 weeks

Long-term Follow-up

Monitoring of overall survival and persistence of ATLCAR.CD30 in peripheral blood

Up to 5 years

Treatment Details

Interventions

• ATLCAR.CD30 Cells (CAR T-cell Therapy)
• Cyclophosphamid (Alkylating agents)
• Fludarabine (Anti-metabolites)

Trial Overview The trial is testing ATLCAR.CD30 Cells combined with Cyclophosphamide and Fludarabine in patients with NSGCT. It's a phase 2 study to see if modified T cells from the patient's blood can fight cancer more effectively when combined with antibodies.

Participant Groups

Group I: ATLCAR.CD30 Experimental Treatment 3 Interventions

Single Group Assignment: Subjects with Nonseminomatous Germ Cell Tumors who meet eligibility criteria for cellular therapy.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Dr. Shelley Earp

UNC Lineberger Comprehensive Cancer Center

Chief Medical Officer since 2018

MD from Johns Hopkins Medical School

Dr. Robert L. Ferris

UNC Lineberger Comprehensive Cancer Center

Chief Executive Officer

PhD in Immunology and MD from Johns Hopkins Medical School; Bachelor's in Chemistry from UNC-Chapel Hill

University Cancer Research Fund at Lineberger Comprehensive Cancer Center

Collaborator

Trials

5

Recruited

150+

Findings from Research

The study demonstrates that CD30-targeted CAR-T cell therapy is effective in treating recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL), showing significant tumor suppression in both laboratory and mouse model experiments.

The engineered 9C11-2 CAR T cells exhibited strong cytotoxic effects against CD30-positive cancer cells, indicating their potential as a promising therapeutic option for patients with this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb. Wu, Y., Chen, D., Lu, Y., et al.[2022]

In a study of 72 patients with extranodal natural killer/T-cell lymphoma (NKTCL), 56% of cases were found to express CD30, which was associated with better responses to non-anthracycline-based therapies.

CD30 positivity, particularly at a cutoff value of 5%, was linked to longer overall survival in patients treated with non-anthracycline chemotherapy, suggesting that CD30 could serve as a valuable prognostic factor and therapeutic target in NKTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic implications of CD30 expression in extranodal natural killer/T-cell lymphoma according to treatment modalities. Kim, WY., Nam, SJ., Kim, S., et al.[2022]

Brentuximab vedotin, a targeted therapy that effectively kills cancer cells expressing CD30, shows promise in treating testicular germ cell tumors (TGCTs), particularly in patients with advanced disease who have limited treatment options.

The study found that brentuximab vedotin works well in combination with certain chemotherapy drugs like etoposide and paclitaxel, but not with cisplatin, which may limit its use in standard treatment regimens for TGCTs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of brentuximab vedotin, alone or in combination with current clinical therapies, in the treatment of testicular germ cell tumors. Yeste-Velasco, M., Guo, T., Mao, X., et al.[2020]

Human teratocarcinoma stem cells, like other pluripotent cells, can develop into various tissues, but the role of growth factors in regulating their growth is not well understood compared to mouse stem cells.

CD30 and its ligand may play a role in identifying stem cell identity and regulating embryonal carcinoma stem cells, but exogenous CD30 ligand does not promote growth in human multipotent stem cells in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD30 and its ligand: possible role in regulation of teratoma stem cells. Pera, MF., Bennett, W., Cerretti, DP.[2019]

CD30-redirected CAR T cells (CD30.CAR T cells) effectively target and kill embryonal carcinoma (EC) cells in vitro and in vivo, demonstrating their potential as a treatment for aggressive testicular germ cell tumors.

These CAR T cells not only attack CD30+ tumor cells but also eliminate surrounding CD30- cells through a mechanism involving Fas/FasL interactions, suggesting a strategy to overcome tumor heterogeneity and enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD30-Redirected Chimeric Antigen Receptor T Cells Target CD30+ and CD30- Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions. Hong, LK., Chen, Y., Smith, CC., et al.[2020]

CAR T cells have shown significant clinical effectiveness in treating blood cancers, but their success in solid tumors has been less impressive, highlighting the need for further research in this area.

While CAR T cell therapy can lead to serious side effects like cytokine release syndrome and neurological toxicity, some theoretical risks have not yet been observed in clinical settings, emphasizing the importance of managing known toxicities for safe treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and management in CAR T-cell therapy. Bonifant, CL., Jackson, HJ., Brentjens, RJ., et al.[2023]

In a phase 1 study involving 12 pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), the autologous CD19-CAR T-cell therapy was well tolerated, with low rates of cytokine release syndrome (6 patients) and neurotoxicity (3 patients).

75% of the patients achieved a minimal residual disease-negative complete response in the bone marrow, although higher disease burden before treatment was linked to more side effects and lower response rates, emphasizing the importance of pre-infusion disease status on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. Talleur, AC., Qudeimat, A., Métais, JY., et al.[2022]

CAR T cell therapy targeting CD19 can effectively treat B cell malignancies but poses safety risks by also destroying healthy B cells that express the same antigen, leading to potential long-term tissue damage.

Research suggests that targeting activation-associated antigens, which are only temporarily present on stem cells, is safer than targeting lineage-associated antigens, which can harm tissue stem cells during their maturation process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells? Hombach, AA., Abken, H.[2017]

Chimeric antigen receptor (CAR) T-cell therapy has shown success in phase 1 clinical trials for targeting and killing tumor cells, but safety concerns like on-target/off-tumor effects and cytokine release syndrome necessitate strategies to mitigate these risks.

Current research is exploring various methods to enhance the safety of CAR T-cell therapy, including pharmacologic therapies, suicide genes, and innovative approaches to restrict cytotoxic effects specifically to cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seatbelts in CAR therapy: How Safe Are CARS? Minagawa, K., Zhou, X., Mineishi, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Prognostic implications of CD30 expression in extranodal natural killer/T-cell lymphoma according to treatment modalities. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The potential of brentuximab vedotin, alone or in combination with current clinical therapies, in the treatment of testicular germ cell tumors. [2020]

4. Denmark pubmed.ncbi.nlm.nih.gov

CD30 and its ligand: possible role in regulation of teratoma stem cells. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

CD30-Redirected Chimeric Antigen Receptor T Cells Target CD30+ and CD30- Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Toxicity and management in CAR T-cell therapy. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells? [2017]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Seatbelts in CAR therapy: How Safe Are CARS? [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Gene-modified T-cell therapy using chimeric antigen receptors for pediatric hematologic malignancies. [2017]

11. United States pubmed.ncbi.nlm.nih.gov

CD30 antigen in embryonal carcinoma and embryogenesis and release of the soluble molecule. [2022]

12. England pubmed.ncbi.nlm.nih.gov

CD30 as a therapeutic target in adult haematological malignancies: Where are we now? [2023]